Representative LAMP1/ThioS/DAPI images in 4- and 12-month AppNL−G−FxMAPT mice demonstrate the sparsity of hypothalamic plaques at the early-stage, and that lysosomal accumulation precedes deposition of β-sheet plaques (Fig. 6M; see also Supplementary Fig. 12 for hippocampal and cortical images), further indicating the autophagic-lysosomal burden in the hypothalamus of the AD mice from early disease stages. The gene discussed is LAMP1; the disease is Alzheimer disease.